Salt sensitivity is a heritable trait that is a hallmark of hypertension in African Americans. Genes encoding adrenergic receptors are candidate loci for the inheritance of this hypertension-related trait because of the role of these receptors in the regulation of renal sodium excretion and vascular tone. This study was performed to determine whether these loci are responsible for some of the phenotypic variation in salt sensitivity. Hypertensive African American probands were ascertained, followed by sequential ascertainment of adult sib pairs among the proband's first, second and third degree relatives. Both hypertensive and normotensive siblings were tested for salt sensitivity by an intravenous sodium- loading, lasix volume-depletion protocol. Genotyping was performed using restriction fragment length polymorphisms in genomic DNA probed with clones containing the beta2- and alpha2c10-adrenergic receptor genes. A total of 109 sib pairs were evaluated. Salt sensitivity was defined as the change in blood pressure in each individual, comparing the sodium-loaded to the volume-depleted state. Systolic pressure decreased by an average of 9.0 + 9%, diastolic pressure by 1.5 + 11%, and mean arterial pressure by 5.0 + 9%. Neither blood pressure nor salt sensitivity were linked to the alpha2c10- adrenergic receptor locus. There was no evidence suggesting that systolic salt sensitivity and baseline blood pressure were linked to the beta2-adrenergic receptor locus. Model-independent sib pair linkage analysis suggested that diastolic blood pressure response to sodium loading/volume depletion is linked to the beta2-adrenergic receptor locus (p< .006). Evidence for linkage was significant at the 0.05 level after adjustment for the number of phenotypic traits examined. Future plans include corroborating these results in a larger sample size, sequencing the beta2-ADR gene to see if sequence variation is associated with salt sensitivity, testing other markers and candidate genes in this population, and identifying other phenotypic subtypes that are linked at this locus.